ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

AIM:To investigate the effects of electroacupuncture at the Taiyang on refractive parameters and the expression of β-catenin and integrin β1 in the ciliary body of mice with form-deprivation myopia(FDM).METHODS:A total of 48 3-week-old healthy C57BL/6J mice were randomly divided into 4 groups: normal control(NC), FDM group, sham acupuncture(sham), and electroacupuncture at Taiyang acupoint(Taiyang), with 12 mice in each group. Mice in the FDM, sham, and Taiyang groups, wore translucent custom-made eye masks on the right eye to induce myopia. The Taiyang group received electroacupuncture stimulation at the Taiyang acupoint, while the sham group underwent non-penetrating stimulation with a blunt wooden stick. No intervention was performed on the NC group. Refraction and axial length were measured by infrared autorefractor and optical coherence tomography(OCT)before modeling and at 4 wk after modeling. The expression levels of β-catenin and integrin β1 in the ciliary body of mice at 4 wk after modeling were detected using quantitative real-time PCR(qPCR)and Western blotting(WB).RESULTS:After modeling for 4 wk, compared with the NC group, the FDM and sham groups showed significantly decreased refractive power(both P<0.05), elongated axial length(both P<0.05), and increased β-catenin and integrin β1 expression. Compared with the FDM and sham groups, the Taiyang group showed significantly increased refractive power(both P<0.05), shortened axial length(both P<0.05), and decreased β-catenin and integrin β1 expression.CONCLUSION:Electroacupuncture stimulation at the Taiyang acupoint effectively delayed the progression of myopia in FDM mice, and this effect may be partially mediated through modulating the expression of β-catenin and integrin β1 in the ciliary body.

Insulin-like growth factor-1(IGF-1)is a multifunctional growth factor which plays an important role in various physiological and pathological processes of the body by regulating biological behaviors such as cell proliferation, differentiation, and migration. Studies have found that abnormal expression of IGF-1 in the retina, sclera and other eye tissues can participate in the occurrence, development and prognosis of various ophthalmic diseases by regulating retinal autophagy flux and angiogenesis, adipogenic differentiation of orbital soft tissues and degradation of scleral extracellular matrix. This paper systematically integrates the expression level changes and mechanism of action of IGF-1 in ophthalmic diseases such as diabetic retinopathy(DR), age-related macular degeneration(ARMD), retinopathy of prematurity(ROP), Graves' ophthalmopathy, myopia, corneal injury and uveal melanoma(UM), and combines the latest clinical and animal experimental evidence to evaluate the bright prospects and potential risks of IGF-1 targeted therapy, in order to provide new ideas and theoretical basis for the prevention and treatment of ophthalmic diseases.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeM^GABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeM^GABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeM^GABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeM^GABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeM^GABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals ; GABAergic Neurons/physiology* ; Male ; Central Amygdaloid Nucleus/physiopathology* ; Hypotension/physiopathology* ; Mice ; Blood Pressure/physiology* ; Mice, Inbred C57BL ; Solitary Nucleus/physiology* ; Photic Stimulation ; Neural Pathways/physiology*

Objective To evaluate the long-term effects of orthokeratology(ortho-k)lenses with different back optical zone diameters(BOZD)on the quality of vision in myopic children.Methods We conducted an exploratory analysis based on a prospective,randomized,double-blind clinical trial,focusing on the parameters related to visual quality.A total of 66 myopic children aged 8 to 12 years were enrolled and randomly assigned to either a 6-mm BOZD ortho-k lens group(the 6 mm group)or a 5-mm BOZD ortho-k lens group(the 5 mm group).The participants were followed up at baseline,and at 1 day,1 week,and 1,3,6,9,and 12 months after lens wearing.Visual quality measurements included uncorrected visual acuity(VA),best corrected VA,contrast sensitivity(CS),high-order aberrations(HOA),modulation transfer function(MTF),Strayer ratio(SR),and visual quality questionnaire.Results A total of 63 children(33 children in the 6 mm group and 30 children in the 5 mm group)completed the study.There were no significant differences in baseline data between the two groups(P>0.05).There were no significant differences in subjective uncorrected VA or best corrected VA between the two groups at any follow-up visit(P>0.05).After wearing the lenses for 3 months,the CS at high spatial frequency(18 cpd)in the 5 mm group was lower than that in the 6 mm group(P=0.015).However,at 12 months,no significant differences in the CS were found between the two groups(P>0.05).The ocular and corneal total HOA,spherical aberration,and coma aberration in both groups increased after wearing the lenses,and the HOA in the 5 mm group was higher than that in the 6 mm group(all P<0.05).After wearing the lenses for 3 months,the MTF and SR values in the 5 mm group were lower than those in the 6 mm group(P<0.05).At 12 months,there was no significant difference between the two groups(P>0.05).The vision-quality-related questionnaire scores showed no significant differences between the two groups(P>0.05).Conclusion In myopic children,wearing ortho-k lenses with different BOZD results in improved subjective satisfaction,with no difference in subjective visual quality.However,objective visual quality declined in both groups,with a greater impact observed in the 5 mm group.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Objective To investigate the effects of different culture conditions(RPMI-1640,DMEM and DMEM/F12 medium)on the passage of MPM cells isolated from the tissues of Malignant pleural mesothelioma(MPM),and to study the effects of CDKN2B on the proliferation,invasion and apoptosis of MPM cells.Methods MPM cells were isolated from MPM tissues and cultured in RPMI-1640,DMEM and DMEM/F12 medium,respectively.Cell proliferation was examined by CCK-8,and the nuclei and chromosomes were observed by Wright-Giemsa staining.Fluorescence intensities of Calretinin,CD141,CK5,EMA and WT-1 were conducted by immunofluorescence assay.The mRNA and protein expression of CDKN2B were detected by RT-qPCR and Western blot,respectively.Transwell was used to detect cell invasion and flow cytometry was used to detect cell apoptosis.Results The established MPM cells showed good viability when passaged to the 10th generation in RPMI-1640,DMEM and DMEM/F12 cultures,and the MPM markers Calretinin,CD141,CK5,EMA and WT-1 were all expressed in the cells.The viability of MPM cells in RPMI-1640 culture medium was relatively stable.CDKN2B was downregulated in MPM cells(P<0.05),and overexpression of CDKN2B significantly suppressed the proliferation(P<0.05),invasion(P<0.05)and epithelial interstitial transformation of MPM cells(P<0.01),and promoted the apoptosis(P<0.01).Conclusion The established MPM cells were stably passaged in RPMI-1640 culture medium,and CDKN2B may be a potential target for the diagnosis and treatment of MPM.